Lymph Node Staging with a Combined Protocol of ¹⁸F-FDG PET/MRI and Sentinel Node SPECT/CT: A Prospective Study in Patients with FIGO I/II Cervical Carcinoma

Abstract

Lymph node metastases (LNM) are present in a minority of patients with early stages of cervical carcinomas. As conventional imaging including PET/CT has shown limited sensitivity, systematic lymphadenectomies are often conducted for staging purposes.Therefore, the aim of this prospective study was to analyze the impact of 18 F-FDG PET/MRI in addition to sentinel node (SLN) biopsy on lymph node status. Methods: 42 women with initial diagnosis of FIGO IA-IIB cervical carcinomas were included between 03/2016-04/2019. Each patient received preoperative whole body 18 F-FDG PET/MRI (Biograph mMR®, Siemens Healthineers) and SLN imaging with SPECT/CT (Discovery 670 Pro®, GE Healthcare) after intracervical injection of 99m Tc-labeled nanocolloid. Systematic Lymphadenectomy and SLN biopsy served as reference standard. Staging in PET/MRI was performed as a consensus of nuclear medicine and radiology experts. Results: One patient was excluded from surgical staging due to newly diagnosed liver metastases in PET/MRI. Overall prevalence of LNM in the remaining 41 patients was 29.3% (12/41). 5/12 patients with LNM solely had small metastases with maximum diameter ≤5mm. Interpretation of PET/MRI as a consensus of experts showed a specificity of 100% (29/29, 95%CI: 88.3-100%) for LNM-staging, but a low sensitivity of 33.3% (4/12, 95%CI: 12.8-60.9%). LN size was the most important factor for the detectability of metastases, since only LNM >5mm could be identified by PET/MRI (sensitivity >5mm: 57.1%; ≤5mm: 0%). Paraaortic LNM were evaluated accurately in 3/4 cases (16 patients with paraaortic LN removal). SLNs were detectable by SPECT/CT in 82.9% of the patients or 69.0% of hemipelvis. In cases with undetectable SLN in SPEC/TCT, malignancy rate was considerably higher (31.2% vs.19.3%). The combination of PET/MRI and SLN SPECT/CT improved the detection of pelvic LNM from 33.3% to 75%. Conclusion: 18 F-FDG PET/MRI is a highly specific Nstaging method and improves LNM detection. Due to the limited sensitivity in frequently occurring small LNM, PET/MRI should be combined with sentinel node mapping. The proposed combined protocol helps to decide whether extensive surgical staging is necessary in patients with FIGO I/II cervical cancer.

Multiparametric Dual-Time-Point [18F]FDG PET/MRI for Lymph Node Staging in Patients with Untreated FIGO I/II Cervical Carcinoma

“…This finding is of high clinical relevance, as a solely visual assessment of [ 18 F]FDG PET comes with insufficient sensitivity for N-staging in G2 tumors. Under consideration of early data, it can be hypothesized that the SLN technique may achieve more accurate N-staging than visual evaluation of [ 18 F]FDG PET/MRI in early-stage G2 carcinoma [ 16 , 27 ]. This is even more important as, currently, in stage T1B1 and lower (i.e., early cervical cancer below 2 cm), LN dissection of only the SLN is currently considered state of the art [ 2 ].…”

“…LN mapping was performed 3–5 h after intracervical injection of ≈ 200 MBq [ 99m Tc]Tc-Nanocolloide at the 3, 6, 9, and 12 o’clock positions. Imaging was performed with a hybrid SPECT/CT scanner (Discovery 670 Pro ® , GE Healthcare, Chicago, IL, USA), as described previously [ 16 ]. An SLN was defined as focal activity enrichment in SPECT in a plausible anatomical region.…”

“…To reduce morbidity, sentinel lymph node (SLN) biopsy was introduced in 1999 for cervical carcinomas, proving to be safe for early-stage cancer in the case of successful SLN labeling [ 2 , 7 , 10 , 11 , 12 , 13 ]. However, even with correct tracer injection, SLN mapping can fail owing to strong venous tracer outflow or a transformation of the tumoral lymphatic drainage in pre-existing lymphatic tumor spread [ 14 , 15 , 16 ]. In addition, parametrial infiltration, while increasing the risk of LNM from 1% to 5–20% and fundamentally changing clinical management, often remains undetected until surgery [ 17 , 18 ].…”

“…In addition, parametrial infiltration, while increasing the risk of LNM from 1% to 5–20% and fundamentally changing clinical management, often remains undetected until surgery [ 17 , 18 ]. Furthermore, the SLN technique was reported to be insufficient for the evaluation of the para-aortic LN status [ 16 , 19 ].…”

“…However, the combination of MRI and [ 18 F]FDG PET ([ 18 F]FDG PET/MRI) improves the diagnostic accuracy in detecting pelvic and para-aortic LNM as well as distant metastases significantly [ 22 ]. Nevertheless, the sensitivity of the visual assessment of [ 18 F]FDG PET/MRI in cervical carcinoma, even by experts, is limited owing to the low tumor-to-background ratio, especially of small LNM [ 16 ]. As histological ultrastaging revealed a much higher prevalence of isolated tumor cells in the LN or micro-LNM in early tumor stages than hitherto expected [ 23 ], the performance of [ 18 F]FDG PET/MRI has to be improved.…”